期刊
FASEB JOURNAL
卷 26, 期 10, 页码 4057-4067出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.12-206656
关键词
HDAC3; mitotic spindle; kinetochore-microtubule attachment; post-translational modification
资金
- U.S. National Institutes of Health (NIH) [IRACDA K12-GM084897, NRSA F31-GM084695]
- NIH [T32-AI07495, T32-DK07696, CA111479, DK53176, AI071130]
- U.S. Department of Defense [PC080847, PC093132]
- Dan L. Duncan Cancer Center
- Alkek Award in Experimental Therapeutics
Protein acetylation has been implicated in playing an important role during mitotic progression. Aurora B kinase is known to play a critical role in mitosis. However, whether Aurora B is regulated by acetylation is not known. Using IP with an anti-acetyl lysine antibody, we identified Aurora B as an acetylated protein in PC3 prostate cancer cells. Knockdown of HDAC3 or inhibiting HDAC3 deacetylase activity led to a significant increase (P < 0.01 and P < 0.05, respectively) in Aurora B acetylation as compared to siLuc or vehicle-treated controls. Increased Aurora B acetylation is correlated with a 30% reduction in Aurora B kinase activity in vitro and resulted in significant defects in Aurora B-dependent mitotic processes, including kinetochore-microtubule attachment and chromosome congression. Furthermore, Aurora B transiently interacts with HDAC3 at the kinetochore-microtubule interface of congressing chromosomes during prometaphase. This window of interaction corresponded with a transient but significant reduction (P=0.02) in Aurora B acetylation during early mitosis. Together, these results indicate that Aurora B is more active in its deacetylated state and further suggest a new mechanism by which dynamic acetylation/deacetylation acts as a rheostat to fine-tune Aurora B activity during mitotic progression.-Fadri-Moskwik, M., Weiderhold, K. N., Deeraksa, A., Chuang, C., Pan, J., Lin, S.-H., Yu-Lee, L.-Y. Aurora B is regulated by acetylation/deacetylation during mitosis in prostate cancer cells. FASEB J. 26, 4057-4067 (2012). www.fasebj.org
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